Individuals with chronic critical limb ischemia (CCLI) suffer from microvascular disease that negatively impacts the success of interventions for limb salvage. Current diagnostic tools are largely limited to assessing blood flow within large vessels. The ultimate goal of this project is to develop a non-invasive optical probe for imaging of microcirculation and tissue metabolism in patients with CCLI. SPECIFIC AIMS: (1) Modify a multi-modal optical instrument for integration with Arterial Spin Labeling MRI. (2) Cross- validation of optical blood flow and MRI perfusion in human muscles. (3) Quantify muscle blood flow, oxygenation, and oxygen consumption in patients with CCLI, and correlate these variables with accepted vascular testing parameters. RESEARCH DESIGN AND METHODS: The lack of portable, noninvasive technologies for monitoring of both blood flow and oxygenation in the deep microcirculation has led us to develop a hybrid optical probe combining, for the first time, diffuse correlation spectroscopy (DCS) for studies of tissue blood flow with diffuse reflectance spectroscopy (DRS) for studies of tissue oxygenation. DRS has been validated in a few studies of deep muscle tissues. The same cannot be said for DCS. The proposed simultaneous MRI/Optical investigation of reactive hyperemia in normal human muscle will validate DCS, and explore possible uses of the combined information for accurate analysis of tissue physiology. For this purpose, a new non-metallic optical probe will be designed and tested to adapt to the MRI. Correlations of the two simultaneous measurements will be investigated. After validating the DCS flow, the first simultaneous all-optical measurements of blood flow and oxygenation will be conducted in the patients with CCLI during cuff occlusion or exercise. Multiple hemodymamic indices will be constructed from these measured variables and then be correlated with accepted vascular testing parameters such as the Ankle- Brachial Index or Toe-Brachial Systolic Index. RELEVANCE: Current diagnostic techniques are inadequate to offer necessary information for the patients with chronic critical limb ischemia when determining limb, salvage procedures or the extent of amputation, causing a serious health concern. The proposed, non- invasive, portable, and inexpensive optical technology may fill in this gap by providing multiple hemodynamic information and by enabling continuous measurements at the bed-side and in.ambulatory care.